Heparin-induced thrombocytopenia
Encyclopedia
Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia
(a low platelet
count), due to the administration of various forms of heparin
, an anticoagulant
. HIT predisposes to thrombosis
, the abnormal formation of blood clots inside a blood vessel
, and when thrombosis is identified the condition is called heparin-induced thrombocytopenia and thrombosis (HITT). HIT is caused by the formation of abnormal antibodies
that activate platelets. If someone receiving heparin develops new or worsening thrombosis, or if the platelet count falls, HIT can be confirmed with specific blood test
s.
The treatment of HIT requires both protection from thrombosis and choice of an agent that will not reduce the platelet count further. Several agents exist for this purpose, mainly lepirudin
and argatroban
. While heparin was discovered in the 1930s, HIT was not reported until the 1960s and 1970s.
or through an intravenous infusion
, and a "low molecular weight" form that is generally given subcutaneously (administered under the skin). Commonly used low molecular weight heparins are enoxaparin
, dalteparin
, and tinzaparin
.
In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia
. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT will therefore not experience any symptoms. Typically the platelet count will fall 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day.
The most common symptom of HIT is enlargement or extension of a previously diagnosed blood clot, or the development of a new blood clot elsewhere in the body. This may take the form of clots either in arteries
or vein
s, causing arterial or venous thrombosis, respectively. Examples of arterial thrombosis are stroke
, myocardial infarction
("heart attack"), and acute leg ischemia. Venous thrombosis may occur in the leg or arm in the form of deep vein thrombosis
(DVT) and in the lung
in the form of a pulmonary embolism
(PE); the latter usually originate in the leg but migrate to the lung.
In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever
, chills
, high blood pressure
, a fast heart rate
, shortness of breath
, and chest pain
. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots
.
. In HIT, the immune system forms antibodies
against heparin when it is bound to a protein called platelet factor 4
(PF4). These antibodies are usually of the IgG
class and their development usually takes about five days. However, those who have been exposed to heparin in the last few months may still have circulating IgG, as IgG-type antibodies generally continue to be produced even when their precipitant has been removed. This is similar to immunity
against certain microorganisms, with the difference that the HIT antibody does not persist more than three months. HIT antibodies have been found in individuals with thrombocytopenia and thrombosis who had no prior exposure to heparin sulfate, but the majority are found in people who are receiving heparin.
The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor
, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia.
Formation of PF4-heparin antibodies is common in people receiving heparin, but only a proportion of these develop thrombocytopenia or thrombosis. This has been referred to as an "iceberg phenomenon".
(which includes a platelet count) on a regular basis while receiving heparin.
However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. A score of 0–8 points is generated; if the score is 0-3, HIT is unlikely. A score of 4–5 indicates intermediate probability, while a score of 6–8 makes it highly likely. Those with a high score may need to be treated with an alternative drug while more sensitive and specific tests for HIT are performed, while those with a low score can safely continue receiving heparin as the likelihood that they have HIT is extremely low.
The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin-PF4 complexes. This may be with a laboratory test of the ELISA
(enzyme-linked immunosorbent assay) type. The ELISA test, however, detects all circulating antibodies that bind heparin-PF4 complexes, and may also falsely identify
antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin
, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories.
If someone has been diagnosed with HIT, some recommend routine Doppler sonography of the leg veins to identify deep vein thromboses, as this is very common in HIT.
Given the fact that HIT predisposes strongly to new episodes of thrombosis, it is not sufficient to simply discontinue the heparin administration. Generally, an alternative anticoagulant is needed to suppress the thrombotic tendency while the generation of antibodies stops and the platelet count recovers. To make matters more complicated, the other most commonly used anticoagulant, warfarin
, should not be used in HIT until the platelet count is at least 150 x 10^9/L because there is a very high risk of warfarin necrosis
in people with HIT who have low platelet counts. Warfarin necrosis is the development of skin gangrene in those receiving warfarin or a similar vitamin K inhibitor. If the patient was receiving warfarin at the time when HIT is diagnosed, the activity of warfarin is reversed with vitamin K
. Transfusing platelets is discouraged, as there is a theoretical risk that this may worsen the risk of thrombosis; the platelet count is rarely low enough to be the principal cause of significant hemorrhage.
Three agents are used to provide anticoagulation in patients with strongly suspected or proven HIT: danaparoid
, lepirudin
, and argatroban
. These are alternatives to heparin therapy. Not all agents are registered in all countries. For instance, argatroban is not used in the United Kingdom and danaparoid is not available in the United States.
According to systematic review
, patients treated with lepirudin
for HIT showed a relative risk reduction
of clinical outcome (death, amputation, etc.) to be 0.52 and 0.42 when compared to patient controls. In addition, patients treated with argatroban
for HIT showed a relative risk reduction
of the above clinical outcomes to be 0.20 and 0.18.
, have a higher risk, while the risk is very low in women just before and after giving birth. Some studies have shown that HIT is less common in those receiving low molecular weight heparin.
Initially, various theories existed about the exact cause of the low platelets in HIT. Gradually, evidence accumulated on the exact underlying mechanism, and diagnostic tests for the condition emerged in the 1980s. Treatment was initially limited to aspirin and warfarin, but the 1990s saw the introduction of a number of agents that could provide anticoagulation without a risk of recurrent HIT. Older terminology distinguishes between two forms of heparin-induced thrombocytopenia: type 1 (mild, non-immune mediated and self-limiting fall in platelet count) and type 2, the form described above. Currently, the term HIT is used without a modifier to describe the immune-mediated severe form.
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
(a low platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
count), due to the administration of various forms of heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
, an anticoagulant
Anticoagulant
An anticoagulant is a substance that prevents coagulation of blood. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders. Some anticoagulants are used in medical equipment, such as test tubes, blood transfusion bags, and renal dialysis...
. HIT predisposes to thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
, the abnormal formation of blood clots inside a blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
, and when thrombosis is identified the condition is called heparin-induced thrombocytopenia and thrombosis (HITT). HIT is caused by the formation of abnormal antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
that activate platelets. If someone receiving heparin develops new or worsening thrombosis, or if the platelet count falls, HIT can be confirmed with specific blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s.
The treatment of HIT requires both protection from thrombosis and choice of an agent that will not reduce the platelet count further. Several agents exist for this purpose, mainly lepirudin
Lepirudin
Lepirudin is an anticoagulant that functions as a direct thrombin inhibitor.Brand name: Refludan, Generic: Lepirudin rDNA for injection.Lepirudin is a recombinant hirudin derived from yeast cells. It is almost identical to...
and argatroban
Argatroban
Argatroban is an anticoagulant that is a small molecule direct thrombin inhibitor. In 2000, argatroban was licensed by the Food and Drug Administration for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia...
. While heparin was discovered in the 1930s, HIT was not reported until the 1960s and 1970s.
Signs and symptoms
Heparin may be used for both prevention and the treatment of thrombosis. It exists in two main forms: an "unfractionated" form that can be injected under the skinSubcutaneous injection
A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, collectively referred to as the...
or through an intravenous infusion
Intravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
, and a "low molecular weight" form that is generally given subcutaneously (administered under the skin). Commonly used low molecular weight heparins are enoxaparin
Enoxaparin
Enoxaparin is a low molecular weight heparin marketed under the trade names Lovenox and Clexane, among others. It is an anticoagulant used to prevent and treat deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection...
, dalteparin
Dalteparin
Dalteparin is a low molecular weight heparin. It is marketed as Fragmin by Pfizer Inc. Like other low molecular weight heparins, dalteparin is used for prophylaxis or treatment of deep vein thrombosis and pulmonary embolism....
, and tinzaparin
Tinzaparin
Tinzaparin is an antithrombotic drug in the heparin group. It is a low molecular weight heparin marketed as Innohep worldwide. It has been approved by the U.S. Food and Drug Administration for once daily treatment and prophylaxis of deep vein thrombosis and pulmonary embolism...
.
In HIT, the platelet count in the blood falls below the normal range, a condition called thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
. However, it is generally not low enough to lead to an increased risk of bleeding. Most people with HIT will therefore not experience any symptoms. Typically the platelet count will fall 5–14 days after heparin is first given; if someone has received heparin in the previous three months, the fall in platelet count may occur sooner, sometimes within a day.
The most common symptom of HIT is enlargement or extension of a previously diagnosed blood clot, or the development of a new blood clot elsewhere in the body. This may take the form of clots either in arteries
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....
or vein
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...
s, causing arterial or venous thrombosis, respectively. Examples of arterial thrombosis are stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
, myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
("heart attack"), and acute leg ischemia. Venous thrombosis may occur in the leg or arm in the form of deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a blood clot in a deep vein. Deep vein thrombosis commonly affects the leg veins or the deep veins of the pelvis. Occasionally the veins of the arm are affected...
(DVT) and in the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
in the form of a pulmonary embolism
Pulmonary embolism
Pulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
(PE); the latter usually originate in the leg but migrate to the lung.
In those receiving heparin through an intravenous infusion, a complex of symptoms ("systemic reaction") may occur when the infusion is started. These include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, chills
Rigor (medicine)
Rigor is a shaking occurring during a high fever. It occurs because cytokines and prostaglandins are released as part of an immune response and increase the set point for body temperature in the hypothalamus....
, high blood pressure
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, a fast heart rate
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, shortness of breath
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
, and chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...
. This happens in about a quarter of people with HIT. Others may develop a skin rash consisting of red spots
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
.
Mechanism
Heparin occurs naturally in the human body, but the development of HIT antibodies suggests heparin sulfate is sometimes treated as a foreign "non-self" substance by the immune systemImmune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
. In HIT, the immune system forms antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
against heparin when it is bound to a protein called platelet factor 4
Platelet factor 4
Platelet factor 4 is a small cytokine belonging to the CXC chemokine family that is also known as chemokine ligand 4 . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like...
(PF4). These antibodies are usually of the IgG
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
class and their development usually takes about five days. However, those who have been exposed to heparin in the last few months may still have circulating IgG, as IgG-type antibodies generally continue to be produced even when their precipitant has been removed. This is similar to immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
against certain microorganisms, with the difference that the HIT antibody does not persist more than three months. HIT antibodies have been found in individuals with thrombocytopenia and thrombosis who had no prior exposure to heparin sulfate, but the majority are found in people who are receiving heparin.
The IgG antibodies form a complex with heparin and PF4 in the bloodstream. The tail of the antibody then binds to the FcγIIa receptor
FCGR2A
Low affinity immunoglobulin gamma Fc region receptor II-a is a protein that in humans is encoded by the FCGR2A gene.-Interactions:FCGR2A has been shown to interact with PIK3R1 and Syk.-Further reading:- External links :...
, a protein on the surface of the platelet. This results in platelet activation and the formation of platelet microparticles, which initiate the formation of blood clots; the platelet count falls as a result, leading to thrombocytopenia.
Formation of PF4-heparin antibodies is common in people receiving heparin, but only a proportion of these develop thrombocytopenia or thrombosis. This has been referred to as an "iceberg phenomenon".
Diagnosis
HIT may be suspected if blood tests show a falling platelet count in someone receiving heparin, even if the heparin has already been discontinued. Professional guidelines recommend that people receiving heparin have a complete blood countComplete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
(which includes a platelet count) on a regular basis while receiving heparin.
However, not all people with a falling platelet count while receiving heparin turn out to have HIT. The timing, severity of the thrombocytopenia, the occurrence of new thrombosis, and the presence of alternative explanations, all determine the likelihood that HIT is present. A commonly used score to predict the likelihood of HIT is the "4 Ts" score introduced in 2003. A score of 0–8 points is generated; if the score is 0-3, HIT is unlikely. A score of 4–5 indicates intermediate probability, while a score of 6–8 makes it highly likely. Those with a high score may need to be treated with an alternative drug while more sensitive and specific tests for HIT are performed, while those with a low score can safely continue receiving heparin as the likelihood that they have HIT is extremely low.
- Thrombocytopenia: 2 points if the fall in platelet count is >50% of the previous value, or the lowest count (nadir) is 20–100 × 109/liter. 1 point if the fall is 30–50% or the nadir is 10–19 × 109/liter. No points if the fall is less than 30% or the nadir is <10 × 109/liter.
- Timing: 2 points if the fall is between days 5–10 after commencement of treatment. 1 point if the fall is after day 10. If someone has been exposed to heparin within the last 30 days and then has a drop in platelet count within a day of reexposure, 2 points are given. If the previous exposure was 30–100 days ago, 1 point. If the fall is early but there has been no previous heparin exposure, no points.
- Thrombosis: 2 points in new proven thrombosis, skin necrosis (see below), or systemic reaction. 1 point if progressive or recurrent thrombosis, silent thrombosis or red skin lesions. No points if there are no symptoms.
- Alternative cause possible: 2 points if no other cause, 1 point if there is a possible alternative cause, no points if there is a definite alternative cause.
The first screening test in someone suspected of having HIT is aimed at detecting antibodies against heparin-PF4 complexes. This may be with a laboratory test of the ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
(enzyme-linked immunosorbent assay) type. The ELISA test, however, detects all circulating antibodies that bind heparin-PF4 complexes, and may also falsely identify
Type I and type II errors
In statistical test theory the notion of statistical error is an integral part of hypothesis testing. The test requires an unambiguous statement of a null hypothesis, which usually corresponds to a default "state of nature", for example "this person is healthy", "this accused is not guilty" or...
antibodies that do not cause HIT. Therefore, those with a positive ELISA are tested further with a functional assay. This test uses platelets and serum from the patient; the platelets are washed and mixed with serum and heparin. The sample is then tested for the release of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, a marker of platelet activation. If this serotonin release assay (SRA) shows high serotonin release, the diagnosis of HIT is confirmed. The SRA test is difficult to perform and is usually only done in regional laboratories.
If someone has been diagnosed with HIT, some recommend routine Doppler sonography of the leg veins to identify deep vein thromboses, as this is very common in HIT.
Treatment
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
, should not be used in HIT until the platelet count is at least 150 x 10^9/L because there is a very high risk of warfarin necrosis
Warfarin necrosis
Warfarin-induced skin necrosis is a condition in which skin and subcutaneous tissue necrosis occurs due to acquired protein C deficiency following treatment with anti-vitamin K anticoagulants .Warfarin necrosis is a rare but severe complication of treatment with warfarin or related...
in people with HIT who have low platelet counts. Warfarin necrosis is the development of skin gangrene in those receiving warfarin or a similar vitamin K inhibitor. If the patient was receiving warfarin at the time when HIT is diagnosed, the activity of warfarin is reversed with vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
. Transfusing platelets is discouraged, as there is a theoretical risk that this may worsen the risk of thrombosis; the platelet count is rarely low enough to be the principal cause of significant hemorrhage.
Three agents are used to provide anticoagulation in patients with strongly suspected or proven HIT: danaparoid
Danaparoid
Danaparoid sodium is an anticoagulant that works by inhibiting activated factor X .Danaparoid is considered a "low molecular weight heparin" by some sources, but is chemically distinct from heparin and thus has little cross-reactivity in heparin-intolerant patients.It consists of a mixture of...
, lepirudin
Lepirudin
Lepirudin is an anticoagulant that functions as a direct thrombin inhibitor.Brand name: Refludan, Generic: Lepirudin rDNA for injection.Lepirudin is a recombinant hirudin derived from yeast cells. It is almost identical to...
, and argatroban
Argatroban
Argatroban is an anticoagulant that is a small molecule direct thrombin inhibitor. In 2000, argatroban was licensed by the Food and Drug Administration for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia...
. These are alternatives to heparin therapy. Not all agents are registered in all countries. For instance, argatroban is not used in the United Kingdom and danaparoid is not available in the United States.
According to systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
, patients treated with lepirudin
Lepirudin
Lepirudin is an anticoagulant that functions as a direct thrombin inhibitor.Brand name: Refludan, Generic: Lepirudin rDNA for injection.Lepirudin is a recombinant hirudin derived from yeast cells. It is almost identical to...
for HIT showed a relative risk reduction
Relative risk reduction
In epidemiology, the relative risk reduction is a measure calculated by dividing the absolute risk reduction by the control event rate.The relative risk reduction can be more useful than the absolute risk reduction in determining an appropriate treatment plan, because it accounts not only for the...
of clinical outcome (death, amputation, etc.) to be 0.52 and 0.42 when compared to patient controls. In addition, patients treated with argatroban
Argatroban
Argatroban is an anticoagulant that is a small molecule direct thrombin inhibitor. In 2000, argatroban was licensed by the Food and Drug Administration for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia...
for HIT showed a relative risk reduction
Relative risk reduction
In epidemiology, the relative risk reduction is a measure calculated by dividing the absolute risk reduction by the control event rate.The relative risk reduction can be more useful than the absolute risk reduction in determining an appropriate treatment plan, because it accounts not only for the...
of the above clinical outcomes to be 0.20 and 0.18.
Epidemiology
The exact number of cases of HIT in the general population is unknown. What is known is that women receiving heparin after a recent surgical procedure, particularly cardiothoracic surgeryCardiothoracic Surgery
Cardiothoracic surgery is the field of medicine involved in surgical treatment of diseases affecting organs inside the thorax —generally treatment of conditions of the heart and lungs .-Cardiac / Thoracic:...
, have a higher risk, while the risk is very low in women just before and after giving birth. Some studies have shown that HIT is less common in those receiving low molecular weight heparin.
History
While heparin was introduced for clinical use in the late 1930s, new thrombosis in people treated with heparin was not described until 1957, when vascular surgeons reported the association. The fact that this phenomenon occurred together with thrombocytopenia was reported in 1969; prior to this time, platelet counts were not routinely performed. A 1973 report established HIT as a diagnosis, as well as suggesting that its features were the result of an immune process.Initially, various theories existed about the exact cause of the low platelets in HIT. Gradually, evidence accumulated on the exact underlying mechanism, and diagnostic tests for the condition emerged in the 1980s. Treatment was initially limited to aspirin and warfarin, but the 1990s saw the introduction of a number of agents that could provide anticoagulation without a risk of recurrent HIT. Older terminology distinguishes between two forms of heparin-induced thrombocytopenia: type 1 (mild, non-immune mediated and self-limiting fall in platelet count) and type 2, the form described above. Currently, the term HIT is used without a modifier to describe the immune-mediated severe form.